Fig.43.10 ).Prolongedhypercortisolismcanleadtomanifestationsofdiabetesmellitus.Becauseofsuppressionoftheimmunesystemcausedbyglucocorticoids,patientsaremoresusceptibletoinfection.Themineralocorticoidactivitiesofglucocorticoidsandthepossibleincreaseinaldosteronesecretionproducesaltretentionandsubsequentwaterretentionthatresultinhypertension.Excessiveandrogensecretioninwomencanproducehirsutism,malepatternbaldness,andclitoralenlargement(adrenogenitalsyndrome).
AnyenzymeblockagethatdecreasescortisolsynthesiswillincreaseACTHsecretionandproduceadrenalhyperplasia.Themostcommonformofcongenitaladrenalhyperplasiaisduetodeficiencyoftheenzyme21-hydroxylase (CYP21). Theseindividualscannotproducenormalquantitiesofcortisol,deoxycortisol, DOC,corticosterone,oraldosterone(see
Figs.
43.8 43.10C ).BecauseofimpairedcortisolproductionandresultantelevatedACTHlevels,steroidogenesisisstimulated,therebyincreasingthesynthesisproducts“upstream”ofthemissingenzyme,aswellasproductsofthezonareticularis.Becausethelatterincludetheadrenalandrogens,afemale 1.
The adrenal gland is composed of a cortex that is of mesodermal origin and a medulla that is of neuroectodermal origin. The cortex produces steroid hormones, and the medulla produces catecholamines.
2.
The rate-limiting enzymes in medullary catecholamine synthesis are tyrosine hydroxylase and dopamine β-hydroxylase, which are induced by sympathetic stimulation, and phenylethanolamine-Nmethyltransferase, which is induced by cortisol.
3.
Catecholamines increase serum glucose and fatty acid levels. They stimulate gluconeogenesis, glycogenolysis, and lipolysis. Catecholamines increase cardiac output but have selective effects on blood flow to different organs.
4.
Pheochromocytoma is a tumor of chromaffin tissue that produces excessive quantities of catecholamines. Symptoms of pheochromocytoma are often sporadic and include hypertension, headaches, sweating, anxiety, palpitations, chest pain, and orthostatic hypotension.
5.
The adrenal cortex displays clear structural and functional zonation: the zona glomerulosa produces the mineralocorticoid aldosterone, the zona fasciculata produces the glucocorticoid cortisol, and the zona reticularis produces the weak androgens DHEA and DHEAS.
6.
Cortisol binds to the glucocorticoid receptor. During stress, cortisol increases blood glucose by increasing gluconeogenesis in the liver and breaking muscle protein down to supply gluconeogenic precursors. Cortisol also decreases glucose uptake by muscle and adipose tissue and has permissive actions on glucagon and catecholamines. Cortisol has multiple effects on other tissue. From a pharmacological point of view, the most important is the immunosuppressive/ antiinflammatory effect.
7.